The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling

S100B is frequently elevated in malignant melanoma. A regulatory mechanism was uncovered here in which elevated S100B lowers mRNA and secreted protein levels of interleukin-6 (IL6) and inhibits an autocrine loop whereby IL6 activates STAT3 signaling. Our results showed that S100B affects IL6 expression transcriptionally. S100B was shown to form a calcium-dependent protein complex with the p90 ribosomal S6 kinase (RSK), which in turn sequesters RSK into the cytoplasm. Consistently, S100B inhibition was found to restore phosphorylation of a nuclear located RSK substrate, CREB, which is a potent transcription factor for IL6 expression. Thus, elevated S100B reduces IL6-STAT3 signaling via RSK signaling pathway in malignant melanoma. Indeed, the elevated S100B levels in malignant melanoma cell lines correspond to low levels of IL6 and p-STAT3.

Download Full-text

Characterization of Arabidopsis calcium-dependent protein kinases: activated or not by calcium?

Biochemical Journal ◽

10.1042/bj20112072 ◽

2012 ◽

Vol 447 (2) ◽

pp. 291-299 ◽

Cited By ~ 59

Author(s):

Marie Boudsocq ◽

Marie-Jo Droillard ◽

Leslie Regad ◽

Christiane Laurière

Keyword(s):

Protein Kinases ◽

Calcium Binding ◽

Molecular Mechanisms ◽

Calcium Sensitivity ◽

In Planta ◽

Calcium Dependent ◽

Dependent Protein ◽

Biochemical Level ◽

Calcium Dependent Protein Kinases ◽

Ef Hands

CDPKs (calcium-dependent protein kinases), which contain both calmodulin-like calcium binding and serine/threonine protein kinase domains, are only present in plants and some protozoans. Upon activation by a stimulus, they transduce the signal through phosphorylation cascades to induce downstream responses, including transcriptional regulation. To understand the functional specificities of CDPKs, 14 Arabidopsis CPKs (CDPKs in plants) representative of the three main subgroups were characterized at the biochemical level, using HA (haemagglutinin)-tagged CPKs expressed in planta. Most of them were partially or mainly associated with membranes, in agreement with acylation predictions. Importantly, CPKs displayed highly variable calcium-dependences for their kinase activities: seven CPKs from subgroups 1 and 2 were clearly sensitive to calcium with different intensities, whereas six CPKs from subgroup 3 exhibited low or no calcium sensitivity to two generic substrates. Interestingly, this apparent calcium-independence correlated with significant alterations in the predicted EF-hands of these kinases, although they all bound calcium. The noticeable exception, CPK25, was calcium-independent owing to the absence of functional EF-hands. Taken together, the results of the present study suggest that calcium binding differentially affects CDPK isoforms that may be activated by distinct molecular mechanisms.

Download Full-text

Calcium-Binding Properties of a Calcium-Dependent Protein Kinase from Plasmodium falciparum and the Significance of Individual Calcium-Binding Sites for Kinase Activation

Biochemistry ◽

10.1021/bi00178a031 ◽

1994 ◽

Vol 33 (12) ◽

pp. 3714-3721 ◽

Cited By ~ 56

Author(s):

Yi Zhao ◽

Sabine Pokutta ◽

Patrik Maurer ◽

Meinrad Lindt ◽

Richard M. Franklin ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Binding Sites ◽

Calcium Binding ◽

Dependent Protein Kinase ◽

Binding Properties ◽

Kinase Activation ◽

Calcium Dependent ◽

Dependent Protein ◽

Calcium Binding Sites ◽

Calcium Dependent Protein Kinase

Download Full-text

Molecular Players of EF-hand Containing Calcium Signaling Event in Plants

International Journal of Molecular Sciences ◽

10.3390/ijms20061476 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1476 ◽

Cited By ~ 9

Author(s):

Tapan Mohanta ◽

Dhananjay Yadav ◽

Abdul Khan ◽

Abeer Hashem ◽

Elsayed Abd_Allah ◽

...

Keyword(s):

Calcium Signaling ◽

Protein Kinases ◽

Calcium Binding ◽

Life Forms ◽

Terrestrial Environment ◽

Calcium Dependent ◽

Ef Hand ◽

Dependent Protein ◽

Calcium Dependent Protein Kinases ◽

Ef Hands

Ca2+ is a universal second messenger that plays a pivotal role in diverse signaling mechanisms in almost all life forms. Since the evolution of life from an aquatic to a terrestrial environment, Ca2+ signaling systems have expanded and diversified enormously. Although there are several Ca2+ sensing molecules found in a cell, EF-hand containing proteins play a principal role in calcium signaling event in plants. The major EF-hand containing proteins are calmodulins (CaMs), calmodulin like proteins (CMLs), calcineurin B-like (CBL) and calcium dependent protein kinases (CDPKs/CPKs). CaMs and CPKs contain calcium binding conserved D-x-D motifs in their EF-hands (one motif in each EF-hand) whereas CMLs contain a D-x3-D motif in the first and second EF-hands that bind the calcium ion. Calcium signaling proteins form a complex interactome network with their target proteins. The CMLs are the most primitive calcium binding proteins. During the course of evolution, CMLs are evolved into CaMs and subsequently the CaMs appear to have merged with protein kinase molecules to give rise to calcium dependent protein kinases with distinct and multiple new functions. Ca2+ signaling molecules have evolved in a lineage specific manner with several of the calcium signaling genes being lost in the monocot lineage.

Download Full-text

Hypothermal Effects on Expression of Regucalcin, A Calcium Binding Protein, in Livers of Seawater- and Fresh Water-Acclimated Milkfish, Chanos Chanos

10.21203/rs.3.rs-339395/v1 ◽

2021 ◽

Author(s):

Chia-Hao Chang ◽

Tsung-Han Lee

Keyword(s):

Protein Expression ◽

Fresh Water ◽

Calcium Binding ◽

Binding Protein ◽

Calcium Binding Protein ◽

Calcium Dependent ◽

Protein Levels ◽

Binding Function ◽

Mrna And Protein Expression ◽

Apoptotic Pathways

Abstract Regucalcin (RGN) is a calcium-binding protein mainly expressed in the liver. It functions in regulating activities of several calcium-dependent enzymes related to energy metabolism, antioxidant mechanisms, and apoptotic pathways. Previous proteomics analyses revealed downregulation of regucalcin in milkfish livers when acclimated to low temperature (18°C) from normal temperature (28°C). This study first identified the full-length sequence of milkfish regucalcin from livers with high similarity in the protein structure and calcium-binding function compared to the regucalcin of other animals. The mRNA and protein expression of regucalcin in livers of fresh water (FW)- and seawater (SW)-acclimated milkfish under hypothermal acclimation were further analyzed. In FW milkfish, upregulation of regucalcin was found in mRNA and protein levels from two and four days, respectively, to one week after transfer to 18°C for the two. However, in SW milkfish, upregulation of regucalcin occurred quickly and returned to the basal levels in one (mRNA expression) or two days (protein expression) up until one week after transfer. These results suggested potential roles of regucalcin in maintaining calcium homeostasis and its correlation to differential physiological responses in livers of milkfish when they were acclimated to FW and SW.

Download Full-text

Fungal Genomes: Suffering with Functional Annotation Errors

10.21203/rs.3.rs-32751/v1 ◽

2020 ◽

Author(s):

Tapan Kumar Mohanta ◽

Abeer Hashem ◽

Elsayed Fathi Abd_Allah ◽

Ahmed AL Harrasi

Keyword(s):

Calcium Binding ◽

Functional Annotation ◽

Sequence Data ◽

Protein Sequences ◽

Fungal Species ◽

Sequencing Data ◽

Calcium Dependent ◽

Dependent Protein ◽

Ef Hands ◽

Annotation Errors

Abstract Background The genome sequencing data are accumulating at a rapid pace, with the current genome sequence data of more than 5780 species being publicly available at the National Center for Biotechnology Information (NCBI) database alone. However, for the researcher communities to use these data, an error-free functional annotation report is a must. Results Analyses of the whole proteome sequence data of 689 fungal species (7.15 million protein sequences) to find the presence of functional annotation error in several species. Hence, calcium dependent protein kinases (CDPKs) and selenoproteins were targeted for the analysis as it is absent all across the fungi kingdom. The analyses revealed the presence of protein with the functional annotation name CDPK. InterproScan analysis revealed that, none of the protein sequences tagged with name “calcium dependent protein kinase” was found to encode calcium binding EF-hands at the regulatory domain. Similarly, none of a protein sequences with annotation name associated with “selenocysteine” was found to encode Sec (U) amino acid. Conclusion The presence of naming of such functional annotation errors in the fungal kingdom is raised a great concern and need to address it at the earliest possible time.

Download Full-text